Cardiac function and myocardial performance of 24-hour-preserved asphyxiated canine hearts.

A method of 24-hour storage of asphyxiated canine hearts for orthotopic cardiac transplantation was studied to expand the geographical size of the donor pool. Left ventricular function of asphyxiated hearts preserved for 24 hours (group 1, n = 8) was compared with that of hearts donated on-site (group 2, n = 5). Group 1 donors were pretreated with verapamil hydrochloride, propranolol hydrochloride, and prostacyclin. The donor hearts were perfused with warm blood cardioplegia in situ after 10 minutes of asphyxiation and then perfused with cold crystalloid cardioplegia for 2 hours. The hearts were excised and stored in ice-cold University of Wisconsin solution for 22 hours. At orthotopic transplantation, coronary perfusion with warm blood cardioplegia was performed before the graft aorta was unclamped. Conventional cardiac variables (eg, cardiac output and maximum rate of rise of left ventricular pressure), myocardial performance, and diastolic compliance of grafted hearts were assessed 1 hour after weaning from bypass. All recipients in both groups were easily weaned from cardiopulmonary bypass without inotropic agents, and there were no significant differences in cardiac variables between the two groups. These results strongly suggest that cadaver hearts can be preserved for 24 hours with satisfactory cardiac function.     

Successful cardiac preservation for 12 hours using nondepolarizing cold cardioplegia. A canine model

Abstract Isolated canine hearts were preserved for 12 h at 5 °C followed by normothermic reperfusion for 2 h. Dogs were divided into two groups: group 1 ( n = 7) received a nondepolarizing preservation solution in multidose, and group 2 ( n = 6) received single-flushed University of Wisconsin (UW) solution, both administered in multidose fashion. At the end o reperfusion, the myocardial adenosine triphosphate concentration and left ventricular systolic and diastolic function were preserved better in group 1 than in group 2. Myocardial mitochondrial ultra-tructural integrity was identical in the two groups. These results suggested that in a 124 heart preservation, nondepolarizing solution administered in multidose fashion protects the myocardium from the deleterious effects of hypothermia and cardioplegia better than UW solution.     

The effectiveness of ischemic preconditioning on myocardial protection and comparison with K(+) cardioplegia

The purpose of this study is to investigate the effects of ischemic preconditioning on myocardial protection and to compare this method to K(+) crystalloid cardioplegia. Langendorff perfused isolated working rat hearts were used in the following groups. After 20 min of stabilisation, 30 hearts were divided into three groups. In group I (control, n=10), hearts were arrested with cold (+4 degrees C) Krebs-Henseleit (K-H) solution, in group II (cardioplegia, n=10) hearts were arrested with cold K(+) cardioplegia solution, and in group III (preconditioning, n=10) hearts were subjected to 5 min normothermic ischemia followed by 5 min reperfusion then arrested with cold K-H solution. All hearts were subjected to 30 min of global ischemia (24 degrees C) and 40 min of reperfusion. Hemodynamic measurements were performed with a left ventricular latex balloon using a data acquisition system. Creatine kinase (CK-MB) washout and Troponin I (cTnI) levels were determined from the coronary effluents. There was no significant difference among the three groups in any of the parameters (hemodynamic and biochemical) measured at the end of stabilisation period. During reperfusion, functional recovery and coronary flow were significantly improved in K(+) cardioplegia and preconditioned groups compared with control group. CK-MB washout and cTnI levels were significantly lower in groups II and III compared with group I at the reperfusion. However no significant difference was observed between K(+) cardioplegia and preconditioned groups among biochemical and hemodynamic parameters and coronary flow at the post-ischemic period. In conclusion, ischemic preconditioning is as effective as K(+) cardioplegia on myocardial protection and recovery of myocardial function during reperfusion.     

Low-potassium University of Wisconsin solution for cardioplegia: improved protection of the isolated ischemic neonatal rabbit heart

Recovery of cardiac function and high-energy phosphates following ischemia and reperfusion were determined for hearts perfused with low potassium University of Wisconsin solution, high potassium University of Wisconsin solution, St Thomas' solution, or subjected to hypothermia alone. Isolated hearts were arrested for either 3 h at 15 degrees C or 6 h at 20 degrees C (n = 7 for each group) with one of the four solutions and then reperfused. Aortic flow after ischemic arrest at 20 degrees C was 40.3 +/- 13.3%, 79.3 +/- 10.0%, 64.3 +/- 11.9% and 43.9 +/- 15.9% of control values for high potassium University of Wisconsin solution, low potassium University of Wisconsin solution, St Thomas' solution and hypothermia alone, respectively. Similar results were observed in hearts subjected to ischemic arrest at 15 degrees C. Myocardial adenosine triphosphate and creatine phosphate after reperfusion tended to be higher in the low potassium University of Wisconsin solution group. It is concluded that low potassium University of Wisconsin solution may provide reliable cardioplegia during surgery that requires prolonged cardiac arrest in neonates and infants.     

The effect of Celsior solution on 12-hour cardiac preservation in comparison with University of Wisconsin solution

BACKGROUND: Celsior is a new extracellular-type preservation solution which has been developed to act not only as a storage medium but also as a perfusion fluid during initial donor heart arrest, poststorage graft reimplantation and early reperfusion. We designed this experimental study to evaluate the effect of the Celsior solution in comparison with the University of Wisconsin solution from the viewpoint of energy depletion. METHODS: Adult mongrel dogs weighing 9 to 13 kg were divided into two groups. In the UW group (n=7), a 4 degrees C University of Wisconsin solution was used for coronary vascular washout and storage following cardiac arrest using a glucose-insulin-potassium solution. In the Celsior group (n=7), the Celsior solution was used to obtain cardiac arrest, coronary vascular washout and storage. High energy phosphate levels and myocardial pH were measured using (31)P-nuclear magnetic resonance spectroscopy immediately after preservation and at 3, 6 and 12 hours after preservation. After 12-hour cold storage, left ventricular free wall tissues were harvested for histological examination. RESULTS: High energy phosphate levels and myocardial pH were significantly better preserved in the Celsior group than in the UW group. In the histological findings, glycogen granules were preserved well in the Celsior group. CONCLUSIONS: We conclude from our study that the Celsior solution is comparable to the University of Wisconsin solution for use in 12-hour heart preservation in canine models.     

Continuous perfusion of donor hearts with oxygenated blood cardioplegia improves graft function

Donor hearts cannot be preserved beyond 6 h using cold storage (CS). Improving preservation methods may permit prolonged storage of donor heart. We compared graft function in large animal model after prolonged preservation (8 h) using continuous perfusion (CP) and CS method. Twenty‐four miniature pigs were used as donors and recipients. Donor hearts were either stored in University of Wisconsin solution (UW solution) for 8 h at 0–4 °C (CS group, n = 6) or were continuously perfused with oxygenated blood cardioplegia at 26 °C for 8 h (CP group, n = 6). After preservation, hearts were transplanted into recipients and reperfused for 3 h. Left ventricular (LV) function, cardiac output (CO), malondialdehyde (MDA) and adenosine triphosphate (ATP) levels, and water content were measured. Although water content of CP hearts was higher than that of CS, LV contractility and diastolic function of CP hearts were superior to those of CS. In addition, CP hearts performed better than CS hearts on CO in working heart state. ATP was better preserved and MDA levels were lower in CP hearts compared with those of CS (P < 0.0001). Donor hearts can be preserved longer using continuous perfusion with oxygenated blood cardioplegia and this method prevents time‐dependent ischemic injury.     

The effect of graft perfusion with warm blood cardioplegia for cadaver heart transplantation

This study was designed to verify the effect of reperfusion of donor hearts in a perfusion apparatus after 60 min of global ischemia prior to heart transplantation. Thirteen dogs were exsanguinated from the femoral artery and cardiac arrest was achieved. The hearts were left in situ at room temperature (25°C)for 60 min. In group A (n=7), the hearts were excised and reperfused 60 min after cardiac arrest in the perfusion apparatus with substrate-enriched warm blood cardioplegia (WBCP) containing a hydroxyl radical scavenger, EPC, followed by 45 min of blood perfusion, Next, the hearts were preserved in cold (4°C) University of Wisconsin (UW) solution. In group B (n=6), the hearts were perfused with cold (4°C) St. Thomas' solution 60 min after cardiac arrest and preserved in cold UW solution. Thereafter, all hearts in both groups were transplanted orthotopically to recipient dogs. In group A, 6 of 7 dogs were weaned from cardiopulmonary bypass (CPB). In group B, only 2 of 6 dogs were weaned from CPB. Moreover, 3 of the 6 hearts in group B did not start beating after transplantation (stone heart). This study suggested reperfusion of the donor heart in the perfusion apparatus with WBCP to be a beneficial preconditioning method when utilizing 60-min arrested hearts for transplantation. This study was supported in part by Senju Pharmaceutical Co. Ltd., Osaka, Japan     

Effects of crystalloid, blood, and University of Wisconsin perfusates on weight, water content, and left ventricular compliance in an edema-prone, isolated porcine heart model.

Coronary perfusion with blood and cardioplegic solutions was examined in isolated, arrested, hypothermic porcine hearts. Myocardial water content, heart weight, and left ventricular diastolic pressure-volume curves were measured before and after coronary perfusion. Statistics were based on exponential curve fitting to pressure-volume data and analysis of variance. Thirty-two pig hearts were divided into five experimental groups and a control group; after control measurements, each experimental group underwent three successive coronary perfusions with 1 L of unmodified blood or a solution of controlled osmolarity, 150 mOsm/L (diluted Plegisol solution), 280 mOsm/L (Plegisol solution and albumin), 334 mOsm/L (University of Wisconsin solution), or 380 mOsm/L (Stanford solution). After each perfusion, measurements were repeated. All experiments were completed within 90 minutes. The first perfusion was delayed 20 minutes after excision of the heart to allow for instrumentation. Each experimental group demonstrated a statistically significant increase in heart weight and myocardial water content and a significant decrease in left ventricular compliance after perfusion. Changes were less pronounced with blood than crystalloids. Edema effects were minimized but not prevented by hyperosmolarity. University of Wisconsin solution appeared unique in minimizing progressive edema after the first perfusion. Over the 81 perfusions studied, changes in left ventricular compliance were linearly related to heart weight and water content. We conclude that in this model, in which edema sensitivity is increased by delayed perfusion and venous occlusion, edema is minimized but not eliminated by whole blood and University of Wisconsin solution. The model appears useful in assessing properties of cardioplegia vehicles intended for use in the injured myocardium.     

A comparison of UW cold storage solution and St. Thomas' solution II: a 31P NMR and functional study of isolated porcine hearts.

Although University of Wisconsin cold storage solution provides excellent preservation for the pancreas, the kidney, and the liver after extended cold ischemic storage, its ability to preserve the heart for extended cold storage periods is not yet proved. This study was carried out to evaluate the effect of University of Wisconsin solution on heart preservation and to compare it to modified St. Thomas' solution II with respect to the capacity to preserve high-energy phosphates and contractile function in pig hearts. Hearts were arrested with either University of Wisconsin cold storage solution or St. Thomas' solution II (10 ml/kg) and kept ischemic at 12 degrees C or 4 degrees C for 8 hours. Functional recovery after the preservation period was assessed by means of ventricular function curves of the isovolumically contracting Langendorff model perfused with modified Krebs-Henseleit solution. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to monitor high-energy phosphates and intracellular pH during preservation and reperfusion. At 12 degrees C, hearts arrested and preserved with University of Wisconsin solution showed a rapid decrease in phosphocreatine and adenosine triphosphate. With St. Thomas' solution, phosphocreatine and adenosine triphosphate decreased slowly. Functional recovery was poorer with University of Wisconsin solution than with St. Thomas' solution. Hearts preserved at 4 degrees C with either solution showed no significant differences in high-energy phosphate content and functional recovery. Rigorous control of the low temperature (4 degrees C) is necessary when University of Wisconsin solution is used for heart preservation.     

Prolonged preservation of the blood-perfused canine heart with glycolysis-promoting solution.

BACKGROUND: Prolonged ischemia and inadequate myocardial preservation remain significant perioperative risk factors in cardiac transplantation. Long-term preservation techniques that have been effective in small rodent hearts have not been as effective in larger animal models or in clinical studies. We developed a cardioplegia solution formulated to promote high-energy phosphate production from glycolysis and determined its efficacy in a blood perfused canine heart model subjected to 24 hours of ischemia. METHODS: Hearts harvested from adult dogs (n = 6 per group) were flushed with a histidine-buffered cardioplegia solution containing glucose or University of Wisconsin solution. The hearts were maintained at 4 degrees C for 24 hours then reperfused with autologous blood. After reperfusion, left ventricular pressures were measured with an intracavitary balloon at varying balloon volumes and compared with control nonischemic hearts. Predicted stroke volume and ejection fraction were calculated at an end-systolic pressure of 70 mm Hg and end-diastolic pressure of 15 mm Hg. RESULTS: Developed pressure was better preserved in the hearts that received histidine-buffered solution (93+/-9 versus 38+/-7 mm Hg, p<0.05), along with a higher end-diastolic volume at 15 mm Hg (31+/-3 versus 22+/-2 mL histidine-buffered versus University of Wisconsin solutions, respectively, p<0.05). Stroke volume and ejection fraction were also higher in the histidine group (17+/-2.5 versus 2.3+/-1.2 mL and 50%+/-3.5% versus 9% +/-4.5%, respectively) in the presence of dobutamine. CONCLUSIONS: The highly buffered glycolysis-promoting cardioplegia solution provided effective preservation of the blood perfused canine heart with superior recovery of pump performance after 24 hours of hypothermic ischemia compared with University of Wisconsin solution in this model.     

A comparative study of Celsior and University of Wisconsin solutions based on 12-hr preservation followed by transplantation in canine models

BACKGROUND: Celsior is a recently developed extracellular-type preservation solution that is effective in organ preservation. This experimental study was designed to compare the effects of Celsior and University of Wisconsin (UW) solutions in myocardial protection, using 12-hour preservation followed by orthotopic transplantation. METHODS: Fourteen pairs of adult mongrel dogs were divided into 2 groups. In the UW group (n = 7), UW solution at 4 degrees C was used for coronary vascular washout and storage following cardiac arrest with glucose-insulin-potassium (GIK) solution. In the Celsior group (n = 7), Celsior solution was used to produce cardiac arrest, for coronary vascular washout, and for storage. After 12-hour cold preservation, orthotopic transplantation was performed under cardiopulmonary bypass (CPB). The rate of recovery (%) of cardiac function of donor hearts was compared 1 and 2 hours after weaning from CPB, and then the transplanted hearts were harvested for histological study. RESULTS: Hemodynamic parameters including cardiac output, left ventricular pressure (LVP), and the maximum rates of positive and negative increase of LVP after transplantation were significantly (p < 0.05) higher in the Celsior group than in the UW group 2 hours after weaning from CPB. The transmission electron microscopic study found that degeneration of the mitochondria in the Celsior group was less extensive than in the UW group. CONCLUSION: Celsior solution enhanced the cardiac function of hearts preserved for 12 hours prior to transplantation compared to UW solution. Our results indicate that Celsior solution is equivalent or superior to UW solution for cardiac preservation.     

University of Wisconsin solution versus crystalloid cardioplegia for human donor heart preservation. A randomized blinded prospective clinical trial.

We have previously shown the safety and efficacy of University of Wisconsin solution for hypothermic preservation of the human donor heart in a pilot group of 16 transplant recipients. The present study is a randomized clinical trial comparing University of Wisconsin solution to conventional preservation using crystalloid cardioplegia and saline storage within a 4-hour limit of ischemia. Heart transplant recipients (n = 42) were randomized into two groups: those receiving hearts preserved by University of Wisconsin solution, the UWS group (n = 22), and those receiving hearts preserved in the conventional manner, the CCS group (n = 20). Recipient age, gender, heart disease, and preoperative inotropic support and donor age, gender, and mean ischemic time in hours (UWS 2 hours 36 minutes, range 1 hour 36 minutes to 2 hours 53 minutes; CCS 2 hours 20 minutes, range 1 hour 20 minutes to 2 hours 44 minutes; p = not significant) were similar. Significant differences observed between the two groups included (1) mean time (minutes) from reperfusion to achieve a stable rhythm, (2) need for intraoperative defibrillations, (3) need for transient cardiac pacing, and (4) integrated postoperative creatinine kinase and aspartate aminotransferase release over 48 hours. There was no difference in postoperative electrocardiogram, endomyocardial biopsy, or hemodynamics. One UWS patient died of sepsis and another of a ruptured cerebral aneurysm. UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared with CCS hearts, hearts preserved in UWS regained electrical activity more rapidly and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long-term survival, to determine the prevalence of rejection and graft atherosclerosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.     

Optimizing probucol administration to preserve left ventricular compliance after reperfusion injury in the heterotopic rat heart isograft.

BACKGROUND: We investigated the optimal method of administering probucol to attenuate reperfusion-induced diastolic abnormalities in the left ventricle of the heterotopically transplanted rat heart isograft. METHODS: We assigned Lewis rats (n = 84) to 7 transplant groups. We arrested 42 hearts using coronary perfusion with hypothermic University of Wisconsin (UW) solution at 60 mm Hg and abdominally isografted the hearts. Neither donors nor recipients in the control group (C-C, n = 6) received probucol. Oral probucol (1% by weight in chow) was fed for 1 month before surgery to the donors only (OP-C, n = 6), the recipients only (C-OP, n = 6), or both (OP-OP, n = 6). We administered an intraperitoneal injection of probucol (300 mg/kg) in 3 ml oil 1 hour before surgery to the donors only (IP-C, n = 6), the recipients only (C-IP, n = 6), or both (IP-IP, n = 6). Transplanted hearts were reperfused for 15 minutes and re-arrested. We also arrested the control recipients' native hearts (native, n = 6). We measured post-mortem left ventricular compliance curves and myocardial water content. RESULTS: The most compliant grafts were in Groups IP-IP, OP-OP, and C-IP. All isograft groups had significantly less left ventricular compliance than did native hearts. Myocardial water content was significantly greater in controls than in natives, OP-OP, and OP-C. CONCLUSIONS: Pre-treatment with intraperitoneal probucol in cardiac isograft recipients combines optimal protection with simple administration when UW solution is used for both arrest and preservation. Further studies of the protective effect of probucol against reperfusion injury in large-animal models are warranted and should use intraperitoneal or intravenous injection in recipients.     

Attenuation of reperfusion injury with probucol in the heterotopic rat cardiac isograft.

BACKGROUND: We tested the hypothesis that pretreatment with the antioxidant probucol attenuates reperfusion-induced diastolic abnormalities in the heterotopic rat cardiac isograft. METHODS: American Cancer Institute rats (n = 48) were divided into 6 groups. Hearts were arrested by coronary perfusion with 3 ml 4 degrees C University of Wisconsin solution at 60 mmHg. Eighteen donor hearts were divided into 3 groups of 6 and arrested either 1 hour after intraperitoneal injection of 3 ml oil with (Prob Tx) or without (Oil Tx) probucol (300 mg/kg) or without injection (Ctrl Tx). After a 90 minute storage period, abdominal isografting was performed with a total ischemic time of 2 hours. Following 15 minutes of blood reperfusion, donor hearts were rearrested and excised. Recipients' native hearts (NH, n = 18) were also arrested. Two additional groups with (Prob NR, n = 6) and without (Ctrl NR, n = 6) probucol pretreatment were arrested and subjected to 2 hours of ischemia without reperfusion. Postmortem LV pressure-volume curves and myocardial water content (MWC) were measured. RESULTS: At each pressure interval normalized LV volume (LVV) was significantly greater for Prob Tx than Oil Tx or Ctrl Tx. All isograft groups had significantly lower LVV at all pressure intervals and higher MWC than non-transplanted hearts. CONCLUSIONS: Pretreatment with probucol attenuates reperfusion-induced decreases in LVV in the heterotopic rat heart isograft model. Probucol, which is orally active in humans, merits further study for its potential to improve myocardial protection during cardiac surgery.     

冷浸泡法保存犬心3 h后原位心脏移植的实验研究

目的 探讨Ｓｔ Ｔｈｏｍａｓ仿细胞外液、Ｃｏｌｌｉｎｓ仿细胞内液及两种液体联合应用在冷浸泡法供心保存中的心肌保护效果。方法 １２只供犬随机平均分为３组;第１组：以Ｓｔ Ｔｈｏｍａｓ液作为停跳液、灌注冲洗液和保存液;第２组：以Ｃｏｌｌｉｎｓ液作为停跳液、灌注冲洗液和保存液;第３组：以ＳｔＴｈｏｍａｓ液作为停跳液、Ｃｏｌｌｉｎｓ液作为灌注冲洗和保存液。将离体共心放入４℃灌注冲洗液中保存３ｈ。观察指标：     

Superiority of the University of Wisconsin solution over simple crystalloid for extended heart preservation. A study of left ventricular pressure-volume relationship.

To compare the effects of the University of Wisconsin solution with those of an extracellular crystalloid solution, Krebs-Ringer bicarbonate, as cardiac preservation media, we studied 35 adult dogs in an isolated heart preparation. Four groups of seven hearts were preserved in University of Wisconsin solution for 6 or 12 hours or in Krebs-Ringer bicarbonate solution for 6 or 12 hours. An additional group of seven hearts with no ischemia was used for a control group. In the four preservation groups, hearts were arrested by electrolyte solution (Normosol with potassium chloride, 20 mEq/L, added, 4 degrees C), flushed with 200 ml of the preservation solution, and then stored in the same solution at 1 degree to 2 degrees C. The hearts were mounted on an isolated heart preparation equipped with a computer-controlled servo-pump system that used a mock arterial system to modulate the aortic input impedance presented to the left ventricle. Left ventricular pressure-volume loops were measured on-line for 2 hours of reperfusion with autologous warm oxygenated blood. Elastance was derived from the end-systolic pressure-volume relationship, and diastolic compliance was derived from the end-diastolic pressure-volume relationship. The total left ventricular performance was assessed by the preload recruitable stroke work area, the slope, and its x-intercept, all of which derived from the stroke work (pressure-volume area)-end-diastolic volume relationship. Extended global ischemia had more deleterious effects on the end-diastolic than the end-systolic pressure-volume relationship. In confirmation with other studies, elastance did not accurately reflect the level of ventricular contractile dysfunction because of the significant amount of diastolic dysfunction. The preservation of myocardial systolic and diastolic functions, as demonstrated by the preload recruitable stroke work area and diastolic compliance, was better in the University of Wisconsin solution groups than in the Krebs-Ringer bicarbonate solution groups after 6 and 12 hours of preservation. In addition, 6 hours of preservation with University of Wisconsin solution maintained normal systolic and diastolic functions as compared with those of the control group. Preservation with University of Wisconsin solution prevented any myocardial edema formation; by contrast, this was significantly increased after 12 hours in Krebs-Ringer bicarbonate solution. Groups preserved with University of Wisconsin solution had less reperfusion injury as evidenced by the release of coronary sinus creatine kinase during reperfusion; they also had improved oxygen use during reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Successful transplantation after long-term preservation of dog hearts.

Nucleoside transport inhibition is a new approach to long-term preservation of donor hearts. To evaluate its effectiveness, the following were tested: 1) the effect of nucleoside transport inhibition on high-energy phosphate content after cardioplegic arrest and during long-term cold storage (group I: cardioplegia, control ]n = 18]; group II: cardioplegia plus nucleoside transport inhibitor [n = 18]); 2) the effect of nucleoside transport inhibition on high-energy phosphates and hemodynamic recovery in a modified blood-perfused Langendorff system (group III: 24-h cold storage followed by reperfusion [n = 6]; group IV: addition of nucleoside transport inhibition to cardioplegia but not during reperfusion [n = 6]; group V: addition of nucleoside transport inhibition during reperfusion [n = 6]; group VI: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 6]); and 3) the effect of nucleoside transport inhibition added to cardioplegia and during reperfusion on high-energy phosphate content and outcome after heart transplantation (group VII: no nucleoside transport inhibitor in cardioplegia and during reperfusion [n = 8]; group VIII: addition of nucleoside transport inhibition to cardioplegia and during reperfusion [n = 8]). The following results were obtained: 1) addition of nucleoside transport inhibition prevented high-energy phosphate depletion during cold storage: after 24 h, adenosine triphosphate content in group I was 9.4 +/- 3.1 mumol/g versus 17.7 +/- 3.6 mumol/g dry weight in group II (P less than 0.05); 2) addition of nucleoside transport inhibition to cardioplegia and during reperfusion resulted in greater high-energy phosphate content (adenosine triphosphate in group III was 7.9 +/- 3.5 mumol/g vs. 17.8 +/- 2.8 mumol/g in group VI [P less than 0.05]) and improved hemodynamics upon reperfusion (hearts in group III did not recover, maximum isometric left ventricular pressure development was 1,635 +/- 577 mmHg/sec in group IV, 1,915 +/- 423 mmHg/sec in group V, and 2,437 +/- 201 mmHg/sec in group VI [P less than 0.05, group VI vs. groups IV and V]); and 3) hearts treated with nucleoside transport inhibition in cardioplegia and during reperfusion (group VIII) could be transplanted successfully in contrast to group VII hearts. These data indicate that nucleoside transport inhibition in dogs is highly effective in long-term preservation of donor hearts.     

Effects of supplemental L-arginine during warm blood cardioplegia.

OBJECTIVES: Effects of supplemental L-arginine, nitric oxide precursor, during warm blood cardioplegia were assessed in the blood perfused isolated rat heart. METHODS: The isolated hearts were perfused with blood at 37 degrees C from a support rat. After 20 minutes of aerobic perfusion, the hearts were arrested for 60 minutes with warm blood cardioplegia given at 20-minute intervals. This was followed by 60 minutes of reperfusion. The hearts were divided into the following three groups according to the supplemental drugs added to the cardioplegic solution. The control group (n = 10) received standard warm blood cardioplegia. The L-ARG group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l). The L-NAME group (n = 10) received warm blood cardioplegia supplemented with L-arginine (3 mmol/l) and L-nitro-arginine methyl ester, a competitive inhibitor of nitric oxide synthase (1 mmol/l). After 60 minutes of cardioplegic arrest, cardiac function, myocardial metabolism and myocardial release of circulating adhesion molecules were measured during reperfusion. RESULTS: Left ventricular end-diastolic pressure was significantly lower (p<0.05) in the L-ARG group than in the control group and the L-NAME group during reperfusion. Isovolumic left ventricular developed pressure, dp/dt and coronary blood flow were significantly greater (p< 0.05) in the L-ARG group during reperfusion. The L-ARG group resulted in early recovery of lactate metabolism during reperfusion. Myocardial release of circulating intercellular adhesion molecule-1 (ICAM-1) and E-selectin were significantly less (p<0.05) in the L-ARG group at 15 minutes of reperfusion. CONCLUSIONS: The results suggest that augmented nitric oxide by adding L-arginine to warm blood cardioplegia can preserve left ventricular function and ameliorate endothelial inflammation. The technique can be a novel cardioprotective strategy in patients undergoing cardiac surgery.     

Successful long-term preservation of the neonatal heart with a modified intracellular solution.

Current methods of myocardial preservation for transplantation are suboptimal. A newly developed intracellular cardioplegic and storage solution (modified University of Wisconsin solution, group 1) was compared in a randomized, blinded fashion with our present clinical protocol, Stanford cardioplegic solution and saline storage (group 2) in an isolated neonatal pig model. After arrest and storage for 12 hours at 4 degrees C, biopsy specimens were taken from six group 1 hearts and five group 2 hearts for examination under an electron microscope and assessment of high-energy phosphate levels and water content. The remainder (group 1, n = 7; group 2, n = 6) were reperfused with blood for 50 minutes, after which function curves were obtained at left ventricular end-diastolic pressures of 3 to 12 mm Hg and biopsy tissue was taken. Eight control hearts (group 3) were cannulated in situ and perfused on the circuit without arrest or intervening ischemia. Stroke and minute work index curves were approximately threefold and fivefold higher for group 1 (modified University of Wisconsin solution) than for group 2 (Stanford), respectively (p less than 0.01). The hearts preserved with University of Wisconsin solution did not differ in function from unpreserved control hearts (group 3). High-energy phosphate levels were better maintained in group 1 than group 2 (p less than 0.05), and water content was lower (p less than 0.01). Semiquantitative grading of electron micrographs paralleled the functional and biochemical results. Conclusion: Modified University of Wisconsin intracellular solution provides markedly better heart preservation than conventionally used cardioplegic and storage solutions.     

Donor heart preservation with the potassium channel opener pinacidil: comparison with University of Wisconsin and St. Thomas' solution.

BACKGROUND: Hyperpolarized arrest with the potassium channel opener pinacidil has been shown to provide effective myocardial protection during short-term global ischemia. This study tested the hypothesis that pinacidil may provide effective long-term protection for heart transplant preservation. METHODS: Four concentrations of pinacidil (50 microM, 100 microM, 0.5 mM, 1.0 mM) mixed in Krebs-Henseleit solution were compared with University of Wisconsin and St. Thomas' Hospital solutions in a Krebs-Henseleit perfused rabbit Langendorff model (n = 6 for each group). Hearts underwent 4 hours of hypothermic (4 degrees C) storage. Over a wide range of volumes, left ventricular systolic function, diastolic compliance, and coronary flow were measured prior to and following storage. Time to mechanical and electrical arrest, and post-ischemic percent tissue water were also measured. RESULTS: Pinacidil 0.5 mM provided the best preservation of post-ischemic systolic function and coronary flow compared with the other pinacidil concentrations and was statistically equivalent to St. Thomas' solution in terms of post-ischemic systolic, diastolic, and flow properties. However, hearts protected with University of Wisconsin solution had significantly better preservation of systolic function and coronary flow. CONCLUSIONS: This investigation demonstrated that pinacidil in Krebs-Henseleit solution possesses efficacy in long-term donor heart preservation. Pinacidil was equivalent to St. Thomas' solution but inferior to University of Wisconsin solution. Hyperpolarized arrest with potassium channel openers may be a novel strategy to improve donor heart preservation.